Montelukast sodium has a chemical name of sodium 1-(((1-(R)-(3-(2-(7-chloro-2-quinolyl)-vinyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio))methyl)cyclopropyl-acetate, and its structure formula as follows:

Montelukast sodium can be useful in treating asthma, and also can be useful as an anti-allergic drug, etc. This compound was first synthesized by Merck Frosst Canada Ltd. located at Quebec, Canada. In the Chinese Patent Application CN1061407A, Merck Frosst Canada Ltd. disclosed the structure and the synthesis method of the compound by reacting 2-(2-3(R)-(3-2-(7-chloro-2-quinolyl)-vinyl)phenyl)-3-(hydroxy)propyl)phenyl) propanol with 1-(mercaptomethyl)-cyclopropylethyl acetate.
CN1420113A disclosed another synthesis method by reacting 2-(2-3(S)-(3-2-(7-chloro-2-quinolyl)-vinyl)phenyl)-3-(sulfydryl)propyl)phenyl)propanol with 2-(1-bromomethyl)-cyclopropylethyl acetate.
CN101081834A disclosed that said compound was prepared by reacting 2-(2-3(R)-(3-2-(7-chloro-2-quinolyl)-vinyl)phenyl)-3-(hydroxy)propyl)phenyl)propanol having a leaving group with lithium salt of 1-(mercaptomethyl)cyclopropylacetate.
Among the synthesis methods for Montelukast sodium disclosed by the prior arts, most of the methods use a basic compound, methyl 2-(2-3(R or S)-(3-2-(7-chloro-2-quinolyl)-vinyl)phenyl)-3-(hydroxy)propyl)phenyl) propanol, as the staring material, which was synthesized from the intermediate compounds, methyl 2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl) phenyl)-3-oxopropyl)benzoate, or methyl 2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-hydroxypropyl)benzoate. In the prior arts, the kind of intermediate compounds was synthesized by the following several approaches:
For example, J. Org. Chem. Vol. 61, No. 10, 1996, 3398-3405 disclosed that 7-chloro-2-vinyl quinoline and methyl 2-(3-(3-bromomethylphenyl)-3-oxopropyl)) benzoate as the staring materials were reacted by a palladium-catalyzed coupling reaction to obtain methyl 2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-oxopropyl)benzoate.
In the method F provided by EP480717, ethyl 3-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-oxopropionate reacted with methyl iodomethylbenzoate, and then decarboxylated, to generate methyl 2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-oxo propyl)benzoate.
In another method K provided by EP480717, 7-chloroquinaldine as the staring material reacted with isophthalaldehyde to generate 3-(2(E)-2-(7-chloroquinazolinyl)vinyl)benzaldehyde, then reacted with vinylmagnesium bromide to perform a Grignard Reaction, and then reacted with ethyl 2-bromobenzoate, to generate methyl 2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-oxopropyl)benzoate.
Among the above stated synthesis methods for preparing the intermediate compounds, expensive metal palladium was often used, thus making the production cost increase; or the Grignard reactions were performed many times, which require strict and complicate reaction conditions and thus need to be strictly controlled, as well as also generated more byproducts undesired; meanwhile, there was a problem that the obtained products cannot be stored for a long time; therefore, the prior synthesis methods were not applicable for mass production.
In addition, although there are many synthesis methods for preparing the above-mentioned Montelukast sodium intermediate in the prior arts, the synthesis methods for another important Montelukast sodium intermediate shown as formula, 1,2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-oxopropyl)phenyl)propanol, were seldom recorded. Under the existence of a chiral reductant, the latter intermediate compound can be selectively converted into a desired chiral mother nucleus, and thus has an extensive prospect of application.

Therefore, there is a need to research and develop a new synthesis method for preparing the Montelukast sodium intermediate shown as formula 1,2-(2-(3-(2-(7-chloro-2-quinolyl)vinyl)phenyl)-3-oxopropyl)phenyl)propanol, which is applicable for mass production.